OBJECTIVE To study the use of ertapenem delivered in an outpatient parenteral antimicrobial therapy (OPAT) hospital-based unit setting for targeted transrectal ultrasound-guided prostate biopsy (TRUSPBx) prophylaxis in the setting of multidrug-resistant (MDR) Escherichia coli rectal colonization. E coli is the pathogen most commonly associated with post-TRUSPBx complications, and there is increasing prevalence of community-associated MDR E coli.METHODS Prospective data analysis of all patients admitted to the OPAT unit for administration of intravenous antibiotics for prophylaxis for TRUSPBx over 18-month period was performed. Patients had identification of MDRE coli in rectal swab cultures and/or intolerance to available oral agents. Microbiologic data and tolerability of administered antibiotics and outcome after TRUSPBx were tabulated.RESULTS Nine patients (median age 74 years) were referred because of antibiotic-resistant E coli from rectal swabs (all fluoroquinolone resistant, 7 MDR). All patients received ertapenem 1 g intravenously 1 day before TRUSPBx and the day of the procedure before TRUSPBx. None of the patients experienced infectious complications immediately after TRUSPBx or several weeks or months later, and no patient was lost to urologic follow-up.CONCLUSION Increasing worldwide reports of prostatitis, urinary tract infections, and septicemia after TRUSPBx because of MDR E coli suggest rectal screening before procedure may be useful in decreasing complications. Targeted prophylaxis in these instances is necessary. Although carbapenems are used for treatment, they are not routinely used for prophylaxis. We report successful use of ertapenem delivered in a hospital-based OPAT unit for TRUSPBx prophylaxis. (C) 2014 Elsevier Inc.

OBJECTIVES: To determine risk factors for ceftazidime-resistant Klebsiella pneumoniae infection and the effect of ceftazidime-resistant K. pneumoniae infection on mortality during an isolated outbreak.DESIGN: Case-control investigation using clinical and molecular epidemiology and prospective analysis of infection control interventions.SETTING: Surgical intensive care unit of a university-affiliated community hospital.PATIENTS: Fourteen case-patients infected with ceftazidime-resistant K. pneumoniae and 14 control-patients.RESULTS: Ten of 14 case-patients had identical strains by pulsed-field gel electrophoresis. Broad-spectrum antibiotic therapy before admission to the unit was strongly predictive of subsequent ceftazidime-resistant K pneumoniae infection. In addition, patients with ceftazidime-resistant K pneumoniae infection experienced increased mortality (odds ratio. 3.77).CONCLUSIONS: Cephalosporin restriction has been shown to decrease the incidence of nosocomial ceftazidime-resistant K. pneumoniae. However, isolated clonal outbreaks may: occur due to lapses in infection control practices. Reinstatement of strict handwashing, thorough environmental cleaning, and repeat education led to termination of the outbreak. A distinct correlation between ceftazidime-resistant K pneumoniae infection and mortality supports the important influence of antibiotic resistance on the outcome of serious bacterial infections.

ABSTRACT Quinolone-resistant Streptococcus agalactiae bacteria were recovered from single-patient isolates and found to contain mutations in the gyrase and topoisomerase IV genes. Pulsed-field gel electrophoresis demonstrated that four isolates from the same long-term care facility were closely related; in seven cases, quinolone-resistant Haemophilus influenzae and S. agalactiae bacteria were isolated from the same patient.

ABSTRACT Stepwise selection of ciprofloxacin-resistant Haemophilus influenzae mutants produced first-, second-, third-, and fourth-step substitutions in GyrA (S84Y), ParC (S84R), GyrA (D88N), and ParC (E88K), respectively. Successive mutations raised the mutant selection window. The wild-type selection window for garenoxacin, levofloxacin, and moxifloxacin was also measured.

Nineteen isolates of carbapenem-resistant Klebsiella species were recovered from 7 hospitals in New York City. Most K. pneumoniae belonged to a single ribotype. Nucleotide sequencing identified KPC-2, a carbapenem-hydrolyzing beta -lactamase. In 3 strains, TEM-30, an inhibitor-resistant beta -lactamase, was detected. Carbapenem-resistant Klebsiella species possessing KPC-2 are endemic in New York City. This study documents the identification of an inhibitor-resistant TEM beta -lactamase in the United States.

We describe a clonal outbreak of quinolone-resistant Haemophilus influenzae (QRHI) from an affiliated long-term care facility (LTCF-A); the outbreak was associated with the clinical use of levofloxacin, which was determined to be a risk factor for acquisition of QRHI. The minimum inhibitory concentration to which 90% of isolates were susceptible (MIC90), as determined by broth microdilution, was >4 microg/mL for levofloxacin, >2 microg/mL for moxifloxacin, >2 microg/mL for gatifloxacin, and 8 microg/mL for gemifloxacin. The MIC90, as determined by Etest (AB Biodisk), was >32 microg/mL for levofloxacin, ciprofloxacin, moxifloxacin, and gatifloxacin. Having been a resident at LTCF-A and having chronic obstructive pulmonary disease were significant risk factors for acquisition of QRHI at our 500-bed hospital (New York Hospital Queens). All QRHI isolates were found to be genetically related by pulsed-field gel electrophoresis, were nontypeable, were susceptible to ceftriaxone and azithromycin, and were negative for beta -lactamase production. Emphasis on patient contact and respiratory isolation and placing colonized or infected patients in cohorts yielded a marked reduction in the prevalence of QRHI at LTCF-A.

ABSTRACT Fluoroquinolone-resistant isolates of Haemophilus influenzae, obtained from a long-term care facility, were examined for nucleotide sequence differences in the quinolone-resistance-determining regions of gyrA, gyrB, parC , and parE . Similarities among the resistant isolates, plus multiple differences with susceptible isolates, suggest clonal dissemination involving two resistant subclones.

Fluoroquinolone-resistant cultures of Streptococcus pneumoniae were isolated from 2 patients who were treated for pneumonia with levofloxacin. Nucleotide sequence analysis of bacterial DNA showed that the isolates contained mutations in both parC (DNA topoisomerase IV) and gyrA (DNA gyrase), which were shown previously to confer fluoroquinolone resistance. With the resistant isolates, the MICs for ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, and trovafloxacin were above the maximal serum drug concentrations reported for standard dosage regimens. In contrast, the MICs for gemifloxacin and moxifloxacin were below the maximal serum concentrations. Increased effectiveness at blocking the growth of resistant mutants should make gemifloxacin and moxifloxacin less likely to allow the enrichment of mutants within susceptible populations. Additional resistance mutations in the isolates were readily obtained by plating on gemifloxacin- or moxifloxacin-containing agar. Thus, neither compound is expected to halt further accumulation of resistance mutations once mutant enrichment has been initiated by less potent derivatives.

Abstract Objective: To assess nosocomial transmission of imipenem-resistant Pseudomonas aeruginosa (IRPA) following bronchoscopy during August through October 1998. Design: Traditional and molecular epidemiological investigation of a case series. Setting: University-affiliated community hospital. Patients: 18 patients with IRPA bronchial-wash isolates. Interventions: We reviewed clinical data, performed environmental cultures and molecular analysis of all IRPA isolates, and observed disinfection of bronchoscopes. Results: Of 18 patients who had IRPA isolated from bronchoscopic or postbronchoscopic specimens, 13 underwent bronchoscopy for possible malignancy or undiagnosed pulmonary infiltrates. Following bronchoscopy, 3 patients continued to have IRPA isolated from sputum and demonstrated clinical evidence of infection requiring specific antimicrobial therapy. The remaining 15 patients had no further IRPA isolated and remained clinically well 3 months following bronchoscopy. Pulsed-field gel electrophoresis revealed that all strains except one were >95% related. STERIS SYSTEM 1 had been implemented in July 1998 as an automatic endoscope reprocessor (AER) for all endoscopes and bronchoscopes. Inspection of bronchoscope sterilization cycles revealed incorrect connectors joining the bronchoscope suction channel to the STERIS SYSTEM 1 processor, obstructing peracetic acid flow through the bronchoscope lumen. No malfunction warning was received, and spore strips remained negative. Conclusions: The similarity of diverse connectors and limited training by the manufacturer regarding AER for bronchoscopes were the two factors responsible for the outbreak. Appropriate connections were implemented, and there was no further bronchoscope contamination. We suggest active surveillance of all bronchoscopy specimen cultures, standardization of connectors of various scopes and automated processors, and systematic education of staff by manufacturers with periodic on-site observation.

Many strains of Acinetobacter baumannii have become resistant to a variety of clinically available antibacterial agents by both intrinsic and extrinsic mechanisms ([4][1], [15][2]). Several investigators have documented multidrug-resistant A. baumannii causing nosocomial infections and have

A multitude of extended spectrum beta-lactamases (ESBLs) have evolved in response to the use of late generation cephalosporins. In those hospitals where Klebsiella pneumoniae and other bacteria possessing these enzymes flourish, many interventions have been applied to reduce this trend. We instituted a policy of class restriction of cephalosporins in our hospital in 1996 that led to a 44% reduction in ceftazidime-resistant K. pneumoniae hospital-wide and an 87% decrease in the surgical intensive care unit. Another interesting outcome of this strategy was the identification of multiresistant K. pneumoniae, which was now susceptible to ceftazidime. Characterization of these novel isolates demonstrated that the TEM-26 enzyme, which was responsible for ceftazidime resistance in our earlier described outbreak, was lacking in most of the isolates examined. Among the remaining ceftazidime-resistant K. pneumoniae, TEM-26 was also absent, and new enzymes that hydrolyze ceftazidime were detected. Loss of ceftazidime-hydrolyzing beta-lactamases was observed after in vitro passage of ceftazidime-resistant K. pneumoniae on antibiotic-free media. These findings suggest that class restriction of cephalosporins may increase susceptibility among extended-spectrum beta-lactamase-producing pathogens.

Eight patients were infected or colonized with imipenem-resistant Klebsiella pneumoniae (IRKP) from December 1994 to November 1995. Initial Klebsiella isolates were susceptible to imipenem but resistant to all cephalosporins, aminoglycosides, and beta-lactam inhibitor combinations. All patients had been in the surgical intensive care unit and had undergone abdominal surgery or tracheostomy during hospitalization. The average age of the patients was 71 years (range, 41-81 years). All patients were treated with imipenem for 5 to 36 days, and IRKP was recovered from each during or after therapy. Pulsed-field gel electrophoresis (PFGE) of the IRKP isolates revealed three distinct clonal patterns. Paired sequential isolates of imipenem-susceptible K. pneumoniae and IRKP from two patients had identical PFGE patterns, suggesting the development of clonal stepwise resistance to imipenem during therapy. Thus, imipenem resistance in Klebsiella may occur when this agent is used for treatment of infection due to ceftazidine- and aminoglycoside-resistant strains.

Increasing prevalence of multidrug-resistant gram-negative organisms has led to a rise in clinically significant infections with these organisms and an increasing therapeutic dilemma. We present a case of a neurosurgical patient who developed ventriculoperitoneal shunt-associated ventriculitis due to ceftazidime-resistant Klebsiella pneumoniae susceptible to cefepime, imipenem, meropenem, and polymyxin B only. Successful management was accomplished by removal of the shunt and therapy with systemic meropenem and intraventricular polymyxin B. Rapid cerebrospinal fluid (CSF) sterilization occurred, with CSF bactericidal titers of 1:32 to 1:128. Polymyxin B should be considered as adjunctive therapy for life-threatening multidrug-resistant gram-negative infections. Prior literature on use of intrathecal polymyxin B in therapy for meningitis supports its potential efficacy.

CONTEXT:Resistance to most or all cephalosporin antibiotics in Klebsiella species has developed in many European and North American hospitals during the past 2 decades.OBJECTIVE:To determine if restriction of use of the cephalosporin class of antibiotics would reduce the incidence of patient infection or colonization by cephalosporin-resistant Klebsiella.DESIGN:A before-after comparative 2-year trial.SETTING:A 500-bed, university-affiliated community hospital in Queens, NY.PATIENTS:All adult medical and surgical hospital inpatients.INTERVENTION:A new antibiotic guideline excluded the use of cephalosporins except for pediatric infection, single-dose surgical prophylaxis, acute bacterial meningitis, spontaneous bacterial peritonitis, and outpatient gonococcal infection. All other cephalosporin use required prior approval by the infectious disease section.MAIN OUTCOME MEASURE:Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period).RESULTS:An 80.1% reduction in hospital-wide cephalosporin use occurred in 1996 compared with 1995. This was accompanied by a 44.0% reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (P<.01), a 70.9% reduction within all intensive care units (P<.001), and an 87.5% reduction within the surgical intensive care unit (P<.001). A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (P<.01). All such isolates except one were susceptible to other antibiotics.CONCLUSION:Extensive cephalosporin class restriction significantly reduced nosocomial, plasmid-mediated, cephalosporin-resistant Klebsiella infection and colonization. This occurred at the price of increased imipenem resistance in P aeruginosa, which remained susceptible to other agents. Thus, an overall reduction in multiply-resistant pathogens was achieved within 1 year.

the foss of an outer membrane protein.

Six Escherichia coli and 12 Klebsiella pneumoniae isolates from a single hospital expressed a common beta-lactamase with a pI of approximately 9.0 and were resistant to cefoxitin and cefotetan (MIC ranges, 64 to > 128 and 16 to > 128 micrograms/ml, respectively). Seventeen of the 18 strains produced multiple beta-lactamases. Most significantly, three K. pneumoniae strains were also resistant to imipenem (MICs, 8 to 32 micrograms/ml). Spectrophotometric beta-lactamase assays with purified enzyme indicated hydrolysis of cephamycins, in addition to cephaloridine and benzylpenicillin. The 4ene encoding the pI 9.0 beta-lactamase (designated ACT-1 for AmpC type) was cloned and sequenced, which revealed an ampC-type beta-lactamase gene that originated from Enterobacter cloacae and that had 86% sequence homology to the P99 beta-lactamase and 94% homology to the partial sequence of MIR-1. Southern blotting revealed that the gene encoding ACT-1 was on a large plasmid in some of the K. pneumoniae strains as well as on the chromosomes of all of the strains, suggesting that the gene is located on an easily mobilized element. Outer membrane protein profiles of the K. pneumoniae strains revealed that the three imipenem-resistant strains were lacking a major outer membrane protein of approximately 42 kDa which was present in the imipenem-susceptible strains. ACT-1 is the first plasmid-mediated AmpC-type beta-lactamase derived from Enterobacter which has been completely sequenced. This work demonstrates that in addition to resistance to cephamycins, imipenem resistance can occur in K. pneumoniae when a high level of the ACT-1 beta-lactamase is produced in combination with the loss of a major outer membrane protein.

The antibacterial, activity of SCH 27899, was compared with vancomycin in vitro against 210 recent clinical isolates representing eight major genera of Gram-positive organisms. MIC(90) values for everninomicin were consistently better than those of vancomycin for all Gram-positive bacteria tested. Although everninomicin was less bactericidal than vancomycin against staphylococci, it was inhibitory against vancomycin-resistant enterococci. This novel antibiotic may, therefore, provide a clinical alternative to penicillin and vancomycin for therapy of Gram-positive infections.

A 46-year-old woman was admitted to the hospital with severe peripheral vascular disease, requiring multiple vascular surgical procedures. During the sixth hospital week, after prior therapy with multiple antibiotics, Enterococcus faecium was isolated as the only organism from an operating room culture of an infected aortic graft. Histological examination of the graft showed infiltration with polymorphonuclear leukocytes. Subsequently, cultures of an infected inguinal wound yielded Enterococcus faecium with mixed bacterial growth. Both isolates of Enterococcus faecium were resistant to all available antimicrobials, including ampicillin, vancomycin, tetracycline, chloramphenicol, and ciprofloxacin. Compassionate use therapy with quinupristin/dalfopristin (RP59500) was administered for 25 days, the patient's clinical condition improved, and wound healing occurred. Transient elevation of serum alkaline phosphatase was noted. This case demonstrates successful eradication of deep VREF infection by quinupristin/dalfopristin with good tolerance of prolonged therapy.